Variant 12-10415652-TTA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000381903.2(KLRC3):c.728_729del(p.Ile243LysfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,608,872 control chromosomes in the GnomAD database, including 85 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 40 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 45 hom. )

Consequence

KLRC3
ENST00000381903.2 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.490

Variant links:

Genes affected

KLRC3 (HGNC:6376): (killer cell lectin like receptor C3) Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. NK cells preferentially express several calcium-dependent (C-type) lectins, which have been implicated in the regulation of NK cell function. KLRC3 is a member of the NKG2 group which are expressed primarily in natural killer (NK) cells and encodes a family of transmembrane proteins characterized by a type II membrane orientation (extracellular C terminus) and the presence of a C-type lectin domain. The NKG2 gene family is located within the NK complex, a region that contains several C-type lectin genes preferentially expressed on NK cells. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

KLRC3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 12-10415652-TTA-T is Benign according to our data. Variant chr12-10415652-TTA-T is described in ClinVar as [Benign]. Clinvar id is 776694.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2109/152282) while in subpopulation AFR AF= 0.0483 (2008/41548). AF 95% confidence interval is 0.0466. There are 40 homozygotes in gnomad4. There are 962 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRC3	NM_002261.3 linkuse as main transcript	c.678+50_678+51del		intron_variant		ENST00000396439.7	NP_002252.2
KLRC3	NM_007333.2 linkuse as main transcript	c.728_729del	p.Ile243LysfsTer10	frameshift_variant	6/6		NP_031359.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRC3	ENST00000381903.2 linkuse as main transcript	c.728_729del	p.Ile243LysfsTer10	frameshift_variant	6/6	1		ENSP00000371328	P2	Q07444-2
KLRC3	ENST00000396439.7 linkuse as main transcript	c.678+50_678+51del		intron_variant		5	NM_002261.3	ENSP00000379716	A2	Q07444-1

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

2107

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.00368

AC:

905

AN:

245718

Hom.:

AF XY:

0.00265

AC XY:

352

AN XY:

132698

show subpopulations

Gnomad AFR exome

AF:

0.0508

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000341

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000629

Gnomad OTH exome

AF:

0.00200

GnomAD4 exome

AF:

0.00135

AC:

1965

AN:

1456590

Hom.:

AF XY:

0.00115

AC XY:

830

AN XY:

724388

show subpopulations

Gnomad4 AFR exome

AF:

0.0503

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.00269

GnomAD4 genome

AF:

0.0138

AC:

2109

AN:

152282

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

962

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0483

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00132

Hom.:

Asia WGS

AF:

0.00144

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over